Drug-resistant efflux pump extrudes antibiotics from cells for survival. Efflux pump inhibitor (EPI) thus becomes an interesting alternative to handle the drug-resistant bacteria. Conessine, a natural steroidal alkaloid from , previously exhibited efflux pump inhibitory potential. Our molecular docking and molecular dynamics (MD) studies provided atomistic information as well as the interaction of conessine with bacterial MexB efflux pump in phospholipid bilayer membrane to further the previous experimental report. Herein, the binding site and proposed mode of action of conessine were identified compared to known/commercial EPIs such as PAβN or designed-synthetic P9D. Our results explained conessine binding mode of action as an effective agent against the MexB efflux pump. The MD simulation also suggested that conessine was able to affect glycine loop (G-loop) flexibility, and the reduced G-loop flexibility due to conessine could hinder an antibiotics extrusion. In addition, our study suggested the conessine core structure buried in a hydrophobic region in the efflux pump similar to other known EPIs. Our finding could cope as a key for the design and development of the conessine derivative as novel EPI against .Communicated by Ramaswamy H. Sarma.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1080/07391102.2020.1828169 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Fungicide resistance in Fusarium species: exploring environmental impacts and sustainable management strategies.
Arch Microbiol
January 2025
Institute for Tropical Biology and Conservation, Universiti Malaysia Sabah, Jalan, UMS, 88400, Kota Kinabalu, Sabah, Malaysia.
The agricultural productivity and world-wide food security is affected by different phytopathogens, in which Fusarium is more destructive affecting more than 150 crops, now got resistance against many fungicides that possess harmful effects on environment such as soil health, air pollution, and human health. Fusarium fungicide resistance is an increasing concern in agricultural and environmental contexts, requiring a thorough understanding of its causes, implications, and management approaches. The mechanisms of fungicide resistance in Fusarium spp.
View Article and Find Full Text PDFUnraveling Antimicrobial Resistance Dynamics in Mycoplasma gallisepticum: Insights Into Antibiotic and Disinfectant Interactions.
Vet Med Sci
January 2025
Department of Veterinary Hygiene and Management, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.
A major risk to the poultry industry is antimicrobial resistance (AMR), specifically with regard to Mycoplasma gallisepticum (MG) infections. The sensitivity patterns of 100 MG isolates to biocides and antibiotics were examined in this study to clarify the interactions between antimicrobial agents and resistance mechanisms. The antimicrobial activity against MG was assessed using broth microdilution, and the results are shown as the minimum inhibitory concentration (MIC) for each strain, the MIC distribution (range), the MIC, and/or the MIC.
View Article and Find Full Text PDFIn vitro evolution of ciprofloxacin resistance in Neisseria commensals and derived mutation population dynamics in natural Neisseria populations.
FEMS Microbiol Lett
January 2025
Rochester Institute of Technology, Thomas H. Gosnell School of Life Sciences, Rochester, NY, USA.
Commensal Neisseria are members of a healthy human oropharyngeal microbiome; however, they also serve as a reservoir of antimicrobial resistance for their pathogenic relatives. Despite their known importance as sources of novel genetic variation for pathogens, we still do not understand the full suite of resistance mutations commensal species can harbor. Here, we use in vitro selection to assess the mutations that emerge in response to ciprofloxacin selection in commensal Neisseria by passaging 4 replicates of 4 different species in the presence of a selective antibiotic gradient for 20 days; then categorized derived mutations with whole genome sequencing.
View Article and Find Full Text PDFA Conjugated Oligomer with Drug Efflux Pump Inhibition and Photodynamic Therapy for Synergistically Combating Resistant Bacteria.
ACS Appl Mater Interfaces
January 2025
Key Laboratory of Analytical Chemistry for Life Science of Shaanxi Province, School of Chemistry and Chemical Engineering, Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, Shaanxi Normal University, Xi'an 710119, P. R. China.
High expression of drug efflux pump makes antibiotics ineffective against bacteria, leading to drug-resistant strains and even the emergence of "superbugs". Herein, we design and synthesize a dual functional o-nitrobenzene (NB)-modified conjugated oligo-polyfluorene vinylene (OPFV) photosensitizer, OPFV-NB, which can depress efflux pump activity and also possesses photodynamic therapy (PDT) for synergistically overcoming drug-resistant bacteria. Upon light irradiation, the OPFV-NB can produce aldehyde active groups to covalently bind outer membrane proteins, such as tolerant colicin (TolC), blocking drug efflux of bacteria.
View Article and Find Full Text PDFTAK-994 Mechanistic Investigation into Drug-Induced Liver Injury.
Toxicol Sci
January 2025
Takeda Development Center Americas, Inc, Cambridge, MA, USA.
The frequency of drug-induced liver injury (DILI) in clinical trials remains a challenge for drug developers despite advances in human hepatotoxicity models and improvements in reducing liver-related attrition in preclinical species. TAK-994, an oral orexin receptor 2 agonist, was withdrawn from phase II clinical trials due to the appearance of severe DILI. Here, we investigate the likely mechanism of TAK-994 DILI in hepatic cell culture systems examined cytotoxicity, mitochondrial toxicity, impact on drug transporter proteins, and covalent binding.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!